Mesenchymal stem cells (MSCs) are being actively explored to regenerate periodontal tissues, soft tissues, and bone in oral and maxillofacial surgery. Periodontal tissues—including gingiva, periodontal ligament (PDL), cementum, and alveolar bone—require true functional regeneration, not just defect filling.
MSCs contribute via two main mechanisms: differentiation into osteoblasts, fibroblasts, and cementoblasts, and secretion of trophic factors and extracellular vesicles that modulate inflammation, stimulate angiogenesis, and recruit the patient’s own repair cells. Periodontal ligament, dental pulp, gingiva, and bone marrow–derived MSCs have demonstrated new bone, cementum, and PDL fiber formation in animal models, especially when combined with scaffolds such as collagen membranes or bone substitutes. Preclinical studies suggest that “site-specific” cells, such as PDL-derived MSCs, may achieve superior regeneration compared with bone marrow MSCs. Early clinical trials indicate improvements in clinical attachment level and probing depth, though sample sizes are still small and protocols vary.
Cell-free approaches using MSC-conditioned medium or exosomes are gaining interest, as they enhance bone fill and PDL regeneration while avoiding the challenges of cell harvesting and survival.
In soft tissue reconstruction, dental and gingival MSCs exhibit strong proliferative and angiogenic capabilities, supporting gingiva and oral mucosa healing and improving graft and implant integration.
Adipose-derived MSCs and buccal fat pad–derived cells are particularly useful for volume restoration and coverage. Their easy harvest and secretion of pro-angiogenic factors enhance vascularization and soft tissue quality around implants or in mucogingival surgery. Additionally, their immunomodulatory effects may stabilize chronic inflammatory conditions such as periodontitis or peri-implantitis, creating a favorable environment for long-term tissue stability.
For bone regeneration in the jaws, MSCs from bone marrow, dental pulp, PDL, periosteum, and buccal fat pad have been applied experimentally and clinically for intrabony periodontal defects, ridge defects, sinus augmentation, and larger craniofacial defects.
When seeded onto scaffolds—calcium phosphate ceramics, xenografts, or collagen matrices—MSCs support predictable bone formation with low donor site morbidity and good implant integration. Systematic reviews indicate that bone marrow and adipose-derived MSCs improve bone volume and density, while dental tissue–derived MSCs show particular promise for smaller intra-alveolar and periodontal defects.
Across all applications, successful MSC therapy relies on standardized, GMP-compliant cell preparation, careful patient and defect selection, and the use of well-designed scaffolds to support engraftment and regeneration.
While current data are promising, larger and long-term clinical trials are needed before MSC-based therapies can become routine care in oral and maxillofacial surgery.
| Indication | Typical goal of MSC use | Citations |
|---|---|---|
| CLI / PAD / diabetic LEVD | Limb salvage, ulcer healing, improved perfusion, pain relief | (Yusoff & Higashi, 2023; Shirbaghaee et al., 2022; Jin et al., 2021; Elshaer et al., 2021; Navarro et al., 2022; Gupta et al., 2013) |
| Coronary artery disease / MI / ischemic HF | Improve LV function, perfusion, symptoms, remodeling | (Guo et al., 2020; Patel et al., 2025; Kumar et al., 2024; Yun & Lee, 2019; Tao et al., 2016; Majka et al., 2017) |
| Ischemic stroke, other cerebrovascular ischemia | Neuroprotection, angiogenesis, functional recovery | (Pan et al., 2023; Kumari et al., 2025; Rinendyaputri et al., 2025) |
Figure: Major vascular indications and therapeutic aims for MSCs.
Guo, Y., Yu, Y., Hu, S., Chen, Y., & Shen, Z. (2020). The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death & Disease, 11. https://doi.org/10.1038/s41419-020-2542-9
Pan, Y., Wu, W., Jiang, X., & Liu, Y. (2023). Mesenchymal stem cell-derived exosomes in cardiovascular and cerebrovascular diseases: From mechanisms to therapy. Biomedicine & Pharmacotherapy, 163, 114817. https://doi.org/10.1016/j.biopha.2023.114817
Patel, T., Mešić, J., Meretzki, S., Bronshtein, T., Brlek, P., Kivity, V., Pancholy, S., Petrović, M., & Primorac, D. (2025). Therapeutic Potential and Mechanisms of Mesenchymal Stem Cells in Coronary Artery Disease: Narrative Review. International Journal of Molecular Sciences, 26. https://doi.org/10.3390/ijms26115414
Yusoff, F., & Higashi, Y. (2023). Mesenchymal Stem/Stromal Cells for Therapeutic Angiogenesis. Cells, 12. https://doi.org/10.3390/cells12172162
Shirbaghaee, Z., Hassani, M., Keshel, S., & Soleimani, M. (2022). Emerging roles of mesenchymal stem cell therapy in patients with critical limb ischemia. Stem Cell Research & Therapy, 13. https://doi.org/10.1186/s13287-022-03148-9
Kumari, K., Verma, K., Sahu, M., Dwivedi, J., Paliwal, S., & Sharma, S. (2025). Emerging role of mesenchymal cells in cardiac and cerebrovascular diseases: Physiology, pathology, and therapeutic implications. Vascular Pharmacology, 107473. https://doi.org/10.1016/j.vph.2025.107473
Jin, L., Wang, X., Qiao, Z., & Deng, Y. (2021). The safety and efficacy of mesenchymal stem cell therapy in diabetic lower extremity vascular disease: a meta-analysis and systematic review. Cytotherapy. https://doi.org/10.1016/j.jcyt.2021.08.001
Elshaer, S., Bahram, S., Rajashekar, P., Gangaraju, R., & El-Remessy, A. (2021). Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases. International Journal of Molecular Sciences, 23. https://doi.org/10.3390/ijms23010249
Rinendyaputri, R., Nainggolan, I., Idrus, H., Noverina, R., Ayuningtyas, W., Huda, F., & Faried, A. (2025). In vitro and In vivo Studies on Mesenchymal Stem Cells for Ischemic Stroke Therapy: A Scoping Review of The Therapeutic Effect. Stem Cells and Cloning: Advances and Applications, 18, 45 - 61. https://doi.org/10.2147/sccaa.s519338
Liang, H., Zhao, B., Ren, Y., Li, P., & Dai, X. (2025). Application of Wharton's Jelly Mesenchymal Stem Cells in Critical Limb Ischemia. Journal of Endovascular Therapy, 15266028251361770. https://doi.org/10.1177/15266028251361770
Kumar, R., Mishra, N., Tran, T., Kumar, M., Vijayaraghavalu, S., & Gurusamy, N. (2024). Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics. Cells, 13. https://doi.org/10.3390/cells13100855
Navarro, L., Chen, X., Viviescas, L., Ardila-Roa, A., Luna-González, M., Sossa, C., & Arango-Rodríguez, M. (2022). Mesenchymal stem cells for critical limb ischemia: their function, mechanism, and therapeutic potential. Stem Cell Research & Therapy, 13. https://doi.org/10.1186/s13287-022-03043-3
Yun, C., & Lee, S. (2019). Enhancement of Functionality and Therapeutic Efficacy of Cell-Based Therapy Using Mesenchymal Stem Cells for Cardiovascular Disease. International Journal of Molecular Sciences, 20. https://doi.org/10.3390/ijms20040982
Gupta, P., Chullikana, A., Parakh, R., Desai, S., Das, A., Gottipamula, S., Krishnamurthy, S., Anthony, N., Pherwani, A., & Majumdar, A. (2013). A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia. Journal of Translational Medicine, 11, 143 - 143. https://doi.org/10.1186/1479-5876-11-143
Tao, H., Han, Z., Han, Z., & Li, Z. (2016). Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications. Stem Cells International, 2016. https://doi.org/10.1155/2016/1314709
Majka, M., Sułkowski, M., Badyra, B., & Musialek, P. (2017). Concise Review: Mesenchymal Stem Cells in Cardiovascular Regeneration: Emerging Research Directions and Clinical Applications. Stem Cells Translational Medicine, 6, 1859 - 1867. https://doi.org/10.1002/sctm.16-0484